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Colorectal Carcinoma FDG PET and Immunoscintigraphy with 99mTc-Labeled Antibody Fragments for Detection of the Recurrence of Colorectal Carcinoma Petra Willkomm, Hans Bender, Michael Bangard, Pan Decker, Frank Gru¨nwald, and Hans-Ju¨rgen Biersack Departments of Nuclear Medicine and Surgery, University of Bonn, Bonn, Germany 36% of patients; regional lymph node metastases are present The aim of this study was to compare FDG PET with a new in 39%, and distant metastases are present in 19%. The monoclonal antibody–based imaging agent that comprises an overall 5-y survival rate after resection is 55%–75%. After anti–carcinoembryonic antigen (CEA) monoclonal antibody FabЈ primary surgery, 30%–40% of patients with resectable fragment directly labeled with 99mTc. Methods: Twenty-eight tumors experience disease relapse within 3 y. patients who were previously treated for colorectal carcinoma Because early detection and management of recurrent and in whom recurrence was suspected were examined with FDG PET and immunoscintigraphy. The most common indica- disease is associated with improved survival, early detection tions were an elevation of serum CEA (13 patients), suggestive of potentially resectable metastases or tumor recurrence lesions documented by CT (9 patients), sonography (4 patients), leads to improved prognosis (2). Serum levels of carcinoem- and severe constipation (2 patients). Planar imaging and SPECT bryonic antigen (CEA) may be used to monitor the presence were performed 4–6 h after intravenous injection of the new of recurrences with a sensitivity of 59% and a specificity of imaging agent. Whole-body PET was performed 45–60 min after 84% but not to localize recurrent lesions (1). intravenous injection of FDG. The findings were confirmed by Multiple imaging methods (sonography, CT, MRI) are conventional diagnostic modalities, surgery, and histology. Results: Histology confirmed local tumor recurrence in 9 of 28 thus used in routine follow-up to detect tumor recurrence, patients. Clinical follow-up or CT confirmed the presence of liver but they have only limited diagnostic accuracy (3–6). metastases in 9 patients and lymph node involvement, lung Identification of a presacral mass by conventional imaging metastases, and bone metastases in 2 patients each. The new does not allow accurate differentiation between scar tissue, agent correctly detected 8 of 9 local recurrences, whereas FDG fibrotic tissue, or tumor recurrence. Therefore, complemen- PET was able to detect all 9 cases and in 1 case was false- tary methods are warranted. FDG PET and immunoscintigra- positive. Liver metastases were confirmed in 9 patients by FDG phy with 99mTc-labeled anti-CEA antigen-binding fragments PET but in only 1 patient by the new agent. Two cases with lymph node metastases and 2 cases with lung metastases were as topofunctional imaging modalities have both been found correctly identified by FDG PET, but none were detected by the suitable, and several groups have shown that FDG uptake new agent. Finally, bone metastases were identified in 1 patient increases in colon and rectal carcinomas (4–13). by FDG PET but not with the new agent, whereas bone marrow Because FDG uptake can be observed in malignant and infiltration (n 5 1) was diagnosed by both imaging modalities. inflammatory lesions (14), the use of more specific tracers Conclusion: These results indicate that FDG PET and 99mTc- such as antibodies seems desirable. Many studies have used Ј labeled anti-CEA Fab are suitable for the diagnosis of local monoclonal antibodies to detect colorectal cancer (15–35). recurrence of colorectal carcinoma but that FDG PET is clearly Ј superior in the detection of distant metastases (liver, bone, and Recently, an (Fab ) antibody fragment specific to CEA that 99m lung) and lymph node involvement. can be labeled with Tc (CEA-Scan; Immunomedics, Inc., Key Words: colorectal cancer; monoclonal antibody FabЈ frag- Morris Plains, NJ) has become commercially available. ments; immunoscintigraphy; FDG PET Thus, specific images with good contrast between tumors J Nucl Med 2000; 41:1657–1663 and normal tissue can be expected (12,29,35). Our aim was to compare the efficacy of FDG PET with that of a 99mTc-labeled anti-CEA monoclonal antibody for the detec- tion of tumor recurrence and systemic spread of colorectal Colorectal cancer, the second leading cause of cancer carcinoma. mortality in the United States (1), has an incidence of MATERIALS AND METHODS approximately 12%–13% and a mortality rate of 10%–11%. At the time of first diagnosis, the disease is localized in only Patients Twenty-eight patients with suspected recurrence of colorectal carcinoma were enrolled and followed up for 6–19 mo. All were Received Sep. 27, 1999; revision accepted Mar. 8, 2000. For correspondence or reprints contact: Petra Willkomm, MD, Department of informed about the nature of the study and had given written Nuclear Medicine, Sigmund-Freud-Str. 25, D-53127 Bonn, Germany. informed consent before the start of immunoscintigraphy or PET. NEW IMAGING AGENT IN COLORECTAL CANCER • Willkomm et al. 1657 TABLE 1 Results for All Patients Local Liver Distant recurrence metastases metastases Patient Age TNM CEA Indications no. Sex (y) Location classification level PET IS PET IS PET IS for study 1 F 57 R pT3 N0 M0 32 TP TP TN TN TN TN CT lesion behind bladder 2 M 54 R pT3 N1 M0 11 FP TN TP FN TN TN CT liver lesion 3 F 37 R pT2 N0 M0 9, 1 TN TN TN TN TN TN CEA level elevation 4 M 34 C.a. pT3 N3 M0 31 TN TN TN TN TP FN CEA level elevation 5 F 63 C.a. pT3 N2 M0 135 TN TN TP FN TN TN CEA level elevation 6 F 69 R pT3 N0 M0 15, 2 TN TN TN TN TN TN CT lesion after radiation 7 M 45 R pT1 N1 M0 365 TN TN TN TN TP TP CEA level elevation 8 M 68 R pT3 N0 M0 NA TP TP TN TN TN TN CT lesion behind bladder 9 F 62 R pT3 N0 M0 3, 4 TN TN TN TN TN TN Suggestive rectal sonog- raphy findings 10 M 70 S pT2 N0 M0 26 TP TP TN TN TN TN CEA level elevation 11 M 58 R pT3 N0 M1 19, 3 TN TN TP FN TN TN CEA level elevation 12 M 78 R pT3 N0 M1 24 TN TN TP FN TN TN CEA level elevation 13 M 65 S pT3 N2 M0 1, 4 TP FN TN TN TN TN Suggestive rectal sonog- raphy findings 14 F 69 R pT2 N0 M0 19 TN TN TN TN TN TN CEA elevation 15 F 71 R pT3 N0 Mx 15 TN TN TP FN TP FN CEA elevation 16 M 71 R pT3 N1 M1 1, 7 TN TN TN TN TN TN CT lesion behind bladder 17 M 61 S pT2 N0 Mx 1, 3 TN TN TN TN TN TN CT liver lesion 18 F 68 R pT3 N0 M0 6, 5 TN TN TN TN TP FN CT lung lesion 19 F 66 R pT4 N3 M0 5, 9 TP TP TP TP TN TN Suggestive sonography findings 20 M 50 R pT2 N0 Mx 1, 9 TN TN TN TN TN TN Constipation 21 M 51 R pT3 N0 Mx NA TP TP TN TN TN TN Constipation 22 F 68 R pT3 N0 Mx 25 TP TP TN TN TN TN CEA elevation 23 F 48 R pT2 N0 M0 13 TP TP TN TN TN TN CEA elevation 24 M 71 S pT3 N0 Mx 36 TN TN TP FN TN TN CEA elevation 25 F 67 R pT2 N0 M0 3, 4 TN TN TP FN TN TN CT liver lesion 26 M 71 R pT3 N1 Mx 1, 7 TN TN TN TN TN TN CT liver lesion 27 F 73 R pT3 N1 Mx 8 TN TN TP FN TN TN CEA level elevation 28 M 76 R pT3 N0 Mx 2, 4 TP TP TN TN TN TN Suggestive rectal sonog- raphy findings TNM 5 tumor node metastasis; IS 5 immunoscintigraphy; R 5 rectum; TP 5 true-positive; TN 5 true-negative; FP 5 false-positive; FN 5 false-negative; C.a. 5 colon ascendens; NA 5 not available; S 5 sigma. Immunoscintigraphy MBq 99mTc anti-CEA antibodies. The study consisted of planar CEA-Scan from a commercially available kit was labeled with images (500,000 counts) of the chest, abdomen, and pelvis in 99mTc according to the manufacturer’s guidelines. Images were anterior and posterior views after bladder voiding. Additionally, obtained with a double-head camera (Prism 2000; Picker Interna- SPECT of the pelvis was performed (3 degrees, 30 s per step, tional, Cleveland, OH) 4–6 h after intravenous injection of 740 step-and-shoot mode, 180° field of view); in 15 patients, SPECT of TABLE 2 Number of Lesions Detected PET/CEA-Scan Finding TP/TP TP/FN TN/FP TN/TN FP/FP FP/TN FN/TP FN/FN Local recurrence 8 1 0 18 0 1 0 0 Liver metastases 1 8 0 19 0 0 0 0 Bone metastases 1 1 0 26 0 0 0 0 Lung metastases 0 2 0 26 0 0 0 0 Lymph node metastases 0 2 0 26 0 0 0 0 TP 5 true-positive; TN 5 true-negative; FP 5 false-positive; FN 5 false-negative. CEA-Scan is manufactured by Immunomedics, Inc. 1658 THE JOURNAL OF NUCLEAR MEDICINE • Vol. 41 • No. 10 • October 2000 the liver was also performed. The data were processed with Local Recurrence Butterworth-filtered backprojection. CEA-Scan was able to correctly detect 8 of 9 cases of FDG PET local recurrence.
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